Heart FailureNCT07429396
Data-Driven Phenotyping in Heart Failure With Preserved Ejection Fraction
An observational study of Heart Failure and Heart Failure, Diastolic, run by Instituto Politécnico de Leiria at 2 sites in Portugal.
Trial summary
The goal of this observational study is to learn how people with Heart Failure with Preserved Ejection Fraction (HFpEF) can be grouped into different "phenotypes" based on their clinical information. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction (HFPEF)
- How many people
- 200 participants
- Where
- 2 sitesPortugal
- Study dates
- 1 Dec 2026to 31 May 2028
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients (≥18 years) with a confirmed diagnosis of heart failure with preserved ejection fraction (LVEF ≥50%) admitted in the Local Health Unit of the Leiria Region since September 2018. The retrospective phase includes electronic health records from approximately 200 patients, used to obtain multimodal datasets for unsupervised clustering. A cross-sectional phase recruits volunteer participants selected for representativeness of the identified phenotypes to undergo cardiopulmonary exercise testing (CPET) for functional characterization. Collected data include sociodemographic variables, clinical history, imaging findings, laboratory biomarkers (e.g., NT-proBNP), therapeutic data and CPET-derived functional parameters.
Who may be able to join
- Retropective observational phase (Phase I):
- Age ≥18 years;
- Established diagnosis of heart failure with preserved ejection fraction (LVEF ≥50%);
- Patients receiving care (outpatient or inpatient) at the Local Health Unit of the Leiria Region (ULS RL) since September 2018.
- Cross-sectional observational phase (Phase II - CPET):
- Age ≥18 years;
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- Established diagnosis of HFpEF;
- Selection as a volunteer representative of phenotypes identified in the retrospective clustering analysis;
- Provision of written informed consent prior to any study-specific procedures.
Who cannot join
- Retropective observational phase (Phase I):
- Incomplete or inadequate medical records preventing full data extraction.
- Cross-sectional observational phase (Phase II - CPET):
- Medical contraindication or physical inability to perform cardiopulmonary exercise testing (CPET);
- Inability to provide informed consent.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Portugal2 sites
Local Health Unit of the Leiria Region
Leiria, Leiria District, 2410-197
Cristiana Fernandes, +351244817000, cristiana.fernandes@chleiria.min-saude.pt
ciTechCare - Center for Innovative Care and Health Technology
Leiria, 2414-016
Maria P S Guarino, PhD, +351914816037, maria.guarino@ipleiria.pt
Rui M Fonseca-Pinto, PhD, +351965632378, rui.pinto@ipleiria.pt
About this study
The goal of this observational study is to learn how people with Heart Failure with Preserved Ejection Fraction (HFpEF) can be grouped into different "phenotypes" based on their clinical information. The researchers want to understand whether these groups have different health profiles and different responses during a cardiopulmonary exercise test (CPET).
The main questions this study aims to answer are:
Read more
- Can clinical data be used to identify meaningful HFpEF phenotypes?
- Do these phenotypes match well-known HFpEF scores, such as the H2FPEF and Heart Failure Association Pre-test Assessment, Echocardiography and Natriuretic Peptide (HFA-PEFF) scores?
- Do people in different phenotypes show different results on a CPET?
Participants will:
- Have their past clinical records reviewed if they were diagnosed with HFpEF at the Local Health Unit of the Leiria Region (ULS RL);
- A smaller group will attend one visit to complete a CPET, which measures how the heart, lungs and muscles respond during exercise.
This study includes adults aged 18 years or older who have HFpEF. The study does not involve any new treatments or experimental drugs.
Read the detailed description
Heart Failure with Preserved Ejection Fraction (HFpEF) is a complex condition, and people with HFpEF can have different symptoms and clinical profiles. Understanding these differences may help improve how the condition is described and studied. This study has two parts: a retrospective analysis and a cross-sectional assessment.
In the retrospective part, the researchers will collect clinical information that was previously recorded in the hospital's clinical records during past hospitalizations for HFpEF at the Local Health Unit of the Leiria Region (ULS RL). The data will be reviewed and prepared for analysis using standard data quality procedures. After the database is complete, the researchers will use data-driven methods to look for patterns among participants, in order to identify groups of people who share similar characteristics ("phenotypes") without setting predefined categories. Methods will include descriptive statistics, correlation analysis and feature selection using algorithmic approaches such as ReliefF. For phenotyping, unsupervised machine-learning techniques including K-means clustering and principal component analysis (PCA) will be applied.
The cross-sectional part will invite a sample of participants selected to represent each phenotype (planned 15 participants for each phenotype) identified in the retrospective analysis. Selected participants will complete a single on-site visit including informed consent verification, a structured clinical review and a standardized cardiopulmonary exercise test (CPET) performed according to local and international guidelines. The CPET procedures will follow the laboratory protocol, namely calibration of equipment, resting measurements, incremental workload protocol, continuous gas exchange, and electrocardiogram (ECG) monitoring. CPET data will be recorded in digital format and transferred securely to the study database.
The study will also evaluate phenotype concordance with widely used HFpEF tools (H2FPEF and HFA-PEFF) and describe differences in physiological responses during CPET across phenotypes, to help clarify how useful they are in describing different forms of HFpEF. Analyses will emphasize exploratory, data-driven evaluation and estimation of effect sizes, consistent with the phenotyping objectives of the study. Where relevant, associations between phenotype membership and CPET variables will be explored descriptively and through correlation-based analyses.
Ethical and data protection procedures are in place. Personal identifiers will be removed and replaced by study ID codes. A linkage file (study ID to personal identifiers) will be stored on an encrypted device with access restricted to the student investigator. Electronic study data will be housed on secure servers with role-based access control. Data will be retained according to institutional policy and relevant legislation. Only de-identified datasets will be used for analysis and sharing. Safety procedures for CPET include pre-test screening for absolute contraindications, continuous ECG and blood pressure monitoring during the test, availability of emergency equipment and immediate clinical oversight by qualified personnel. Adverse events during CPET will be recorded and reported per the Ethics Committee requirements.
By combining clinical record information collected during previous hospitalizations with detailed exercise testing in a selected group, this study aims to provide new insight into the variation that exists among people with HFpEF. The findings may support more personalized approaches in future research.
- Conditions
- Heart Failure, Heart Failure, Diastolic, Heart Failure With Preserved Ejection Fraction (HFPEF)
- Keywords
- Heart Failure, HFpEF, Preserved Ejection Fraction, Phenotyping, Machine Learning, Data-driven clustering, Cardiopulmonary Exercise Testing, H2FPEF score, HFA-PEFF score, Exercise tolerance
- Medical subject headings
- Heart Failure, Heart Failure, Diastolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Observational HFpEF Cohort | Single observational cohort including all adults with an established diagnosis of heart failure with preserved ejection fraction (LVEF ≥50%) who received care at the Local Health Unit of the Leiria Region (ULS RL) since September 2018. Clinical, biochemical, imaging, functional, and therapeutic information recorded during previous hospitalizations will be extracted for retrospective analysis. A subset of participants will later be invited to complete a single cardiopulmonary exercise test (CPET) according to the study protocol. Phenotypes (clusters) will be identified post-hoc using unsupervised machine-learning methods and are not predefined at the time of enrollment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification and characterization of HFpEF phenotypes using multimodal clustering analysis
Identification of distinct phenotypic clusters in patients with heart failure with preserved ejection fraction using unsupervised machine learning applied to multimodal clinical, biochemical, imaging and functional data.
Measured: Up to December 2026 (completion of retrospective data collection and clustering analysis).
Secondary outcomes (3)
Mean peak oxygen uptake (VO₂peak) during cardiopulmonary exercise testing
Peak oxygen uptake (VO₂peak), expressed in mL·kg-¹·min-¹, measured by breath-by-breath gas analysis during maximal cardiopulmonary exercise testing and compared across HFpEF phenotypes.
Measured: December 2026 to July 2027 (single assessment per participant).
Concordance between H2FPEF and HFA-PEFF scores and identified HFpEF phenotypes
Assessment of concordance and discrimination performance of H2FPEF and HFA-PEFF scores in identifying phenotypes derived from data-driven clustering.
Measured: Up to October 2027.
Mean plasma NT-proBNP concentration (pg/mL) by HFpEF phenotypes
Comparison of plasma NT-proBNP concentrations (pg/mL) between HFpEF phenotypes identified by clustering analysis.
Measured: Up to February 2028.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2026
- Study start1 Dec 2026 (estimated)
- Primary completion1 Aug 2027 (estimated)
- Study completion31 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Politécnico de Leiria
- Sponsor type
- University, hospital or other
- Collaborators
- Faculty of Medicine of Universidade de Lisboa (FMUL), Hospital de Santo André, Fundação para a Ciência e a Tecnologia
- Responsible party
- Sponsor
- Investigators
- Rui M Fonseca-Pinto, PhD, Study director, ciTechCare - Center for Innovative Care and Health Technology, Polytechnic of LeiriaJoão C A Morais, PhD, Study director, ciTechCare - Center for Innovative Care and Health Technology, Polytechnic of LeiriaVera L P Geraldes, PhD, Study director, Faculty of Medicine, University of Lisbon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07429396
- Sponsor's protocol ID
- FCT 2023.05000.BDANA
- Status last verified
- Feb 2026
- First submitted
- 12 Jan 2026
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be shared. The dataset contains sensitive clinical and physiological information, including cardiopulmonary exercise test (CPET) variables, with a high risk of reidentification even after de-identification procedures. Institutional policies, local ethics approval, and applicable data protection regulations do not permit external sharing of these data.
Publications
Ferreira JP, Dewan P, Jhund PS, Lorenzo-Almoros A, Duarte K, Petrie MC, Carson PE, McKelvie R, Komajda M, Zile M, Zannad F, McMurray JJV. Covariate adjusted reanalysis of the I-Preserve trial. Clin Res Cardiol. 2020 Nov;109(11):1358-1365. doi: 10.1007/s00392-020-01632-x. Epub 2020 Mar 25.
PubMed 32215700Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C, Ptaszynska A; I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008 Dec 4;359(23):2456-67. doi: 10.1056/NEJMoa0805450. Epub 2008 Nov 11.
PubMed 19001508Cunningham JW, Vaduganathan M, Claggett BL, John JE, Desai AS, Lewis EF, Zile MR, Carson P, Jhund PS, Kober L, Pitt B, Shah SJ, Swedberg K, Anand IS, Yusuf S, McMurray JJV, Pfeffer MA, Solomon SD. Myocardial Infarction in Heart Failure With Preserved Ejection Fraction: Pooled Analysis of 3 Clinical Trials. JACC Heart Fail. 2020 Aug;8(8):618-626. doi: 10.1016/j.jchf.2020.02.007. Epub 2020 May 6.
PubMed 32387067Pereira PMM, Thomaz LA, Tavora LMN, Assuncao PAA, Fonseca-Pinto RM, Paiva RP, Faria SMM. Melanoma classification using light-Fields with morlet scattering transform and CNN: Surface depth as a valuable tool to increase detection rate. Med Image Anal. 2022 Jan;75:102254. doi: 10.1016/j.media.2021.102254. Epub 2021 Oct 7.
PubMed 34649195Grote T, Berens P. Uncertainty, Evidence, and the Integration of Machine Learning into Medical Practice. J Med Philos. 2023 Feb 17;48(1):84-97. doi: 10.1093/jmp/jhac034.
PubMed 36630292Shehab M, Abualigah L, Shambour Q, Abu-Hashem MA, Shambour MKY, Alsalibi AI, Gandomi AH. Machine learning in medical applications: A review of state-of-the-art methods. Comput Biol Med. 2022 Jun;145:105458. doi: 10.1016/j.compbiomed.2022.105458. Epub 2022 Mar 28.
PubMed 35364311Quazi S. Retraction Note: Artificial intelligence and machine learning in precision and genomic medicine. Med Oncol. 2025 Apr 26;42(6):180. doi: 10.1007/s12032-025-02732-2. No abstract available.
PubMed 40281258Bayes-Genis A, Liu PP, Lanfear DE, de Boer RA, Gonzalez A, Thum T, Emdin M, Januzzi JL. Omics phenotyping in heart failure: the next frontier. Eur Heart J. 2020 Sep 21;41(36):3477-3484. doi: 10.1093/eurheartj/ehaa270.
PubMed 32337540Pieske B, Tschope C, de Boer RA, Fraser AG, Anker SD, Donal E, Edelmann F, Fu M, Guazzi M, Lam CSP, Lancellotti P, Melenovsky V, Morris DA, Nagel E, Pieske-Kraigher E, Ponikowski P, Solomon SD, Vasan RS, Rutten FH, Voors AA, Ruschitzka F, Paulus WJ, Seferovic P, Filippatos G. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur Heart J. 2019 Oct 21;40(40):3297-3317. doi: 10.1093/eurheartj/ehz641.
PubMed 31504452Reddy YNV, Carter RE, Obokata M, Redfield MM, Borlaug BA. A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction. Circulation. 2018 Aug 28;138(9):861-870. doi: 10.1161/CIRCULATIONAHA.118.034646.
PubMed 29792299John JE, Claggett B, Skali H, Solomon SD, Cunningham JW, Matsushita K, Konety SH, Kitzman DW, Mosley TH, Clark D 3rd, Chang PP, Shah AM. Coronary Artery Disease and Heart Failure With Preserved Ejection Fraction: The ARIC Study. J Am Heart Assoc. 2022 Sep 6;11(17):e021660. doi: 10.1161/JAHA.121.021660. Epub 2022 Aug 24.
PubMed 36000416Olaniyi KS, Atuma CL, Sabinari IW, Hadiza M, Saidi AO, Akintayo CO, Ajadi IO, Olatunji LA. Restoration of cardiac metabolic flexibility by acetate in high-fat diet-induced obesity is independent of ANP/BNP modulation. Can J Physiol Pharmacol. 2022 Jun 1;100(6):509-520. doi: 10.1139/cjpp-2021-0531. Epub 2022 Apr 8.
PubMed 35395159Brady PF, Chua W, Nehaj F, Connolly DL, Khashaba A, Purmah YJV, Ul-Qamar MJ, Thomas MR, Varma C, Schnabel RB, Zeller T, Fabritz L, Kirchhof PF. Interactions Between Atrial Fibrillation and Natriuretic Peptide in Predicting Heart Failure Hospitalization or Cardiovascular Death. J Am Heart Assoc. 2022 Feb 15;11(4):e022833. doi: 10.1161/JAHA.121.022833. Epub 2022 Feb 3.
PubMed 35112889Shah SJ. BNP: Biomarker Not Perfect in heart failure with preserved ejection fraction. Eur Heart J. 2022 May 21;43(20):1952-1954. doi: 10.1093/eurheartj/ehac121. No abstract available.
PubMed 35301541Shah SJ, Kitzman DW, Borlaug BA, van Heerebeek L, Zile MR, Kass DA, Paulus WJ. Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction: A Multiorgan Roadmap. Circulation. 2016 Jul 5;134(1):73-90. doi: 10.1161/CIRCULATIONAHA.116.021884.
PubMed 27358439